More Cooling May Help After Cardiac Arrest

Action Points

For patients who remain comatose after an out-of-hospital cardiac arrest, setting a lower temperature target for therapeutic hypothermia may provide better protection against neurological damage.

Note that current guidelines state that comatose survivors of an out-of-hospital cardiac arrest should be cooled to 32º C to 34º C (93.2° F) for 12 to 24 hours, but the ideal temperature has not been established.

For patients who remain comatose after an out-of-hospital cardiac arrest, setting a lower temperature target for therapeutic hypothermia may provide better protection against neurological damage, a pilot trial showed.

The percentage of patients who were alive and free from severe dependence 6 months after the arrest was higher among those cooled to 32° C (89.6° F) than among those cooled to 34º C (44.4% versus 11.1%), although, at P=0.12, the difference was not statistically significant, according to Esteban Lopez-de-Sa, MD, of the Hospital Universitario La Paz in Madrid, and colleagues.

However, the difference reached statistical significance for the patients who had an initial shockable rhythm (61.5% versus 15.4%, P=0.029), the researchers reported online in Circulation: Journal of the American Heart Association.

"The benefits observed here merit further investigation in a larger trial in out-of-hospital cardiac arrest patients with different presenting rhythms," they wrote. "With the results obtained, it is now probably justified to also explore the effect of achieving levels less than 32° C."

The findings were also presented at the American Heart Association meeting in Los Angeles, where program chair Elliott Antman, MD, of Harvard Medical School in Boston, said, "I find this extremely encouraging and I look forward to having more trials in this area because I think it's going to help refine this important therapy for our patients who suffer these very serious events."

Guidelines state that comatose survivors of an out-of-hospital cardiac arrest should be cooled to 32º C to 34º C (93.2° F) for 12 to 24 hours, but the ideal temperature has not been established and most attending physicians have chosen to split the difference and cool to 33º C (91.4º F). No clinical trials have compared two different levels of cooling.

Lopez-de-Sa and colleagues conducted a pilot study that included 36 adult patients (mean age 64) who remained comatose following a witnessed out-of-hospital cardiac arrest. The patients were randomized to therapeutic hypothermia with a target of 32º C or 34º C.

They were also stratified according to whether their initial rhythm was shockable (26 patients) or asystole (10 patients).

The patients were sedated and treated with IV cisatracurium to prevent shivering during therapeutic hypothermia. Cooling was achieved by IV infusion of cold saline followed by implantation of a catheter in the inferior vena cava for delivery of refrigerated saline.

The target temperature was maintained for 24 hours, with a controlled rewarming for 12 to 24 hours.

The primary outcome was survival free from severe dependence (a Barthel Index score of 60 points or higher out of 100) at 6 months.

The rate tended to be higher in the patients cooled to the lower temperature in the overall trial population and was significantly higher in those with an initial shockable rhythm.

No patient whose initial rhythm was asystole survived to 6 months, regardless of the level of cooling.

A lower temperature target appeared to be safe, as rates of complications -- including bleeding, infection, renal impairment, and arrhythmia -- were generally similar in the two groups.

Clinical seizures occurred less frequently with the cooler temperature (1 versus 11, P=0.0002) and bradycardia tended to be less frequent at the higher temperature (2 versus 7, P=0.054).

Potassium levels decreased to a greater extent in the patients who were cooled to a lower temperature, but the rate of hypokalemia did not differ between the two groups.

The researchers noted that it was possible that there was a greater apparent benefit with the lower temperature because patients in that group remained cooled for a longer period of time. Although the time spent at the target temperature was the same in both groups, it took longer to reach the cooler temperature and longer to rewarm those patients.

Also, patients assigned to the higher target temperature received fewer resuscitation attempts by bystanders, did not have a return to spontaneous circulation as quickly, and tended to have a worse Glasgow Coma Scale score at admission than those assigned to the lower temperature.

The study was limited, the researchers acknowledged, by the small sample size, the variability of prognosis, the absence of blinding of the target temperature, and the presence of multiple confounding factors.

"Nevertheless," they wrote, "the aim of the study was not to provide information to change clinical practice but to offer a basis for future research."

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